The renal renin-angiotensin system plays an important role in the regulation of the blood pressure, fluid and electrolyte homeostasis, and in the pathogenesis of various types of hypertension. The activity of this system is mainly determined by the rate of renin release by the kidney. Renin release is controlled by many factors, including: (1) the blood pressure in the afferent arterioles (baroreceptor or stretch hypothesis); (2) delivery of sodium and/or chloride to the macula densa (MD); (3) renal nerve sympathetic activity; and (4) local and circulating factors, such as, prostaglandins, angiotensin II, vasopressin, catecholamines and electrolytes. To better understand how the MD participates in the control of renin release, we have recently developed an in vitro preparation that consists of afferent arterioles with or without the MD attached, microdissected from the rabbit kidney. The MD in this preparation has an inhibitory effect on renin release. Using this preparation, and also other microdissected arterioles and segments of the nephron, we propose to study: (1) whether renal microvessels other than the afferent arterioles release renin; (2) whether nephron structures other than the MD also participate in the control of renin release; (3) whether the signal perceived by the MD is changed either in NaI or C1-; (4) the nature of the messages that the MD transmits to the juxtaglomerular cells, by determining; (a) if the MD releases a paracrine hormone(s) into the extracellular space which alters renin release and (b) if adenosine is one of the paracrine hormones; and (5) the role of intracellular cyclic nucleotides in the control of renin release. The new information acquired by these studies will greatly help to understand the control of renin release and, consequently, it may be useful in understanding alterations of the renin-angiotensin system in various physiologica and pathological situations.